Pediatric tuberculosis in a high burden setting: Socio-spatial distribution, blood elements features, and outcomes.

Background: The childhood tuberculosis (TB) epidemic has been long neglected. Data on pediatric tuberculosis is needed to develop effective strategies against TB. Methods: We retrospectively reviewed 200 medical records from children aged 0-15 years who suffered from tuberculosis between 2011 and 2021 in Libreville, Gabon. We collected and analyzed socio-demographic data and clinical data. Results: 141 children files were selected (43 % girls and 57 % boys). The mean age of the patients was 9.2 years (CI: 8.5-10). Sixty per cent (60 %) of cases were from precarious housing areas, 35.34 % from mixed housing areas, and 4.51 % from residential. The cure rate was 75.24 %, 9.52 % relapsed, and 15.24 % died. Deaths were significantly higher in older children (Dunn's post-test p < 0.01). Children who recovered had higher haemoglobin and platelet counts than those who died (Dunn's test: haemoglobin p < 0.0001; thrombocytes p < 0.05). The haemoglobin threshold value of 5.5 g/dL identified children death with up to 80 % sensitivity and 86 % specificity. Thrombocytes count identified children's death with a sensitivity of 80 % and a specificity of 51 %. Conclusion: Precariousness is associated with childhood tuberculosis. The directly observed therapy (DOTS) in older children should be reinforced to limit tuberculosis-associated deaths. Haemoglobin concentration and platelet are vital prognosis markers in pediatric tuberculosis.

Biochemical Alterations Associated With the Severity of COVID-19 in Sub-Saharan Black African Individuals.

BACKGROUND: Biochemical markers are essential in the monitoring and the clinical care of patients as they inform clinicians. Here, we characterized biochemical alterations in sub-Saharan Black African individuals with COVID-19. METHODS: The study includes COVID-19 patients cared for at the Akanda Army Hospital in Libreville (Gabon). A total of 2237 patient records were extracted and reviewed. Patients were classified based on hospital admission (intensive care unit [ICU], internal medicine ward, and outpatient). RESULTS: One thousand six hundred seventy-one were included in the study. ICU patients were significantly older than non-ICU hospitalized patients (P < 0.001) and outpatients (P < 0.0001). Hyperglycemic patients had 6.4 odds of being in ICU (P < 0.0001). Patients with abnormally high urea had 54.7 odds of being in ICU (P < 0.0001). Patients with abnormally high aspartate aminotransferase (AST) (>33 IU/L) had 3.5 odds of being in ICU (P < 0.0001). Hyperlactatemia (>246 IU/L) odds in ICU patients were 14 (P < 0.0001). The odds of abnormally high alkaline phosphatase (ALP) (>147 IU/L) in ICU patients were 4.6 (P < 0.0001). Odds for hypochloremia (<98 mmol/L) were 1.6 in ICU (P < 0.05). Dysnatremia patients (<135 or >145 mmol/L) had 9.5 odds of being found in ICU patients (P < 0.0001). The odds of potassium imbalance (<3.6 or >5 mmol/L) in ICU patients were 12.2 (P < 0.0001). CONCLUSIONS: COVID-19-associated biochemical alterations observed in the Black African population are similar to those observed in other populations, and the association between COVID-19 severity, hyperglycemia, and multi-organ affection is confirmed.

Changes of C-reactive protein and Procalcitonin after four weeks of treatment in patients with pulmonary TB.

Objective: Tuberculosis (TB) remains a public health concern worldwide, affecting millions of people every year. Detailed characterization of disease pathophysiology is key to proper diagnosis, disease progression, or treatment follow-up and evaluation. The present study investigated C-reactive protein and Procalcitonin (PCT) as candidate markers of early treatment response and disease activity. Methods: From September to December 2019, 21 HIV-negative consecutive TB patients were recruited, within the setting of the Gabonese TB specialized hospital and the National Laboratory of Public Health, in a prospective study. CRP and PCT levels were measured by chemiluminescence at diagnosis and 4 weeks following the initiation of anti-TB treatment. Results: The mean concentration of CRP in TB patients was 114.7 mg/L (95 % CI: [83.8-145.6]) at diagnosis and 20.2 mg/L (95 % CI: [14.1-26.4]) 4 weeks following anti-TB treatment. The drop in CRP concentrations between diagnosis, and week 4 following anti-TB treatment showed was significant (p < 0.0001). The average concentration of PCT at the time of diagnosis was 0.3 ng/mL (95 % CI: [0.19-0.41]). PCT Concentration dropped below 0.05 ng/mL 4 weeks following the start of anti-TB treatment (p < 0.01). Conclusion: CRP and PCT are potential TB biomarkers, each, carrying important keys. If the drop in both proteins may indicate a significant reduction of the Mtb burden, the maintenance of CRP above the inflammation threshold could indicate the presence of residual bacilli. However, the clinical translation of the present finding will require more investigation.

Allergen sensitization and polysensitization pattern of adults and children in an urban Sub-Saharan African setting (Libreville, Gabon).

Background: It is believed that allergic diseases are increasing in Africa. However, the health sector in Africa has yet to catch up with this paradigm shift. We looked at the number of patients referred to us for allergy testing and investigated allergen sensitization. Methods: A retrospective analysis was done on 97 serum allergen-specific IgE results collected from patients suspected of having allergies in Libreville from 2018 to 2021. Specific IgE responses to 180 allergens were investigated. The general sensitization patterns were analyzed. Also analyzed were sensitization patterns for adults and children. The difference in the IgE-binding allergen positivity rate between groups was calculated by using the chi-square (χ2) test. Results: The allergens most commonly causing sensitization were from mites (65%), barley (48%), peach (48%), dog and/or cat dander (44%), house dust (44%), peanut (39%), tomato (39%), cockroach (37%), crab (36%), garlic and/or onion (34%), rye (34%), egg white (32%), shrimp (32%), kiwi (32%), soya bean (32%), citrus mix (29%), cheese (27%), milk (27%), walnut (27%), ox-eye daisy (24%) and orchard grass (24%). Moreover, 60% of patients (36 of 60) were polysensitized to inhalant allergens, 53% (31 of 58) were polysensitized to food allergens, and 29% (14 of 48) were polysensitized to inhalant and food allergens; 65% of patients (53 of 81) were sensitized to allergens originating from mites, fungi (including Candida albicans, Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, and Pennicillium notatum), or bacteria (staphylococcal enterotoxin B). Conclusions: The sensitization pattern of allergens in our setting is rich and varied, with a high prevalence of polysensitization.

Circulating anti-SARS-CoV-2 nucleocapsid (N)-protein antibodies and anti-SARS-CoV-2 spike (S)-protein antibodies in an African setting: herd immunity, not there yet!

OBJECTIVE: Herd immunity is achieved when in a population, immune individuals are in a sufficiently large proportion. Neutralizing antibodies specific to SARS-CoV-2 that are produced following infection or vaccination are critical for controlling the spread of COVID-19. The objective of the present work was to investigate the rate of SARS-CoV-2 natural immunization in Gabonese. RESULTS: One thousand, four hundred and ninety two people were enrolled. The overall prevalence of anti-SARS-CoV-2 antibodies was 36.2%. Moreover, 76.4% of people who developed a humoral response to SARS-CoV-2 produced both anti-SARS-CoV-2 N-protein antibodies and anti-SARS-CoV-2 S-protein antibodies, which correspond to 27.7% of the total population. In infants (0-9 month), children (1-17 years) and adults, the prevalence of anti-SARS-CoV-2 antibodies was relatively the same, between 33 and 37% (any antibody types) and between 25 and 28.6% (neutralizing antibodies). In this African context, one-third (1/3) of the screened population was exposed to SARS-CoV-2 and three-quarter (3/4) of those exposed individuals developed neutralizing antibodies against SARS-CoV-2. This data suggest that herd immunity is not yet to be achieved in Gabon.

Evidence and implications of pre-existing humoral cross-reactive immunity to SARS-CoV-2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged throughout the world. Building knowledge around Covid-19 is crucial to devise facts based approaches to respond efficiently against this pandemic. AIM: We aimed to investigate pre-existing humoral cross-reactive immunity to SARS-CoV-2. METHOD: We have tested the reactivity against SARS-CoV-2 nucleocapsid (N) antigen of sera collected from healthy healthcare volunteers in 2014. We assessed immunoglobulins reactive against SARS-CoV-2 N-antigen using a well-validated serological platform; Elecsys assay. RESULTS: Sera from 32 subjects (out of 135 [23.7%]) were reactive to SARS-CoV-2 N-antigen, suggesting the presence of anti-SARS-CoV-2 N-antigen antibodies. CONCLUSION: Although the clinical relevance of the observed reactivity can only be speculated and needs to be investigated, the implication of this finding for coronavirus disease 2019 seroepidemiological survey and vaccines' clinical trials is critical.

Dynamic and features of SARS-CoV-2 infection in Gabon.

In a context where SARS-CoV-2 population-wide testing is implemented, clinical features and antibody response in those infected have never been documented in Africa. Yet, the information provided by analyzing data from population-wide testing is critical to understand the infection dynamics and devise control strategies. We described clinical features and assessed antibody response in people screened for SARS-CoV-2 infection. We analyzed data from a cohort of 3464 people that we molecularly screened for SARS-CoV-2 infection in our routine activity. We recorded people SARS-CoV-2 diagnosis, age, gender, blood types, white blood cells (WBC), symptoms, chronic disease status and time to SARS-CoV-2 RT-PCR conversion from positive to negative. We calculated the age-based distribution of SARS-CoV-2 infection, analyzed the proportion and the spectrum of COVID-19 severity. Furthermore, in a nested sub-study, we screened 83 COVID-19 patients and 319 contact-cases for anti-SARS-CoV-2 antibodies. Males and females accounted for respectively 51% and 49% of people screened. The studied population median and mean age were both 39 years. 592 out of 3464 people (17.2%) were diagnosed with SARS-CoV-2 infection with males and females representing, respectively, 53% and 47%. The median and mean ages of SARS-CoV-2 infected subjects were 37 and 38 years respectively. The lowest rate of infection (8%) was observed in the elderly (aged > 60). The rate of SARS-Cov-2 infection in both young (18-35 years old) and middle-aged adults (36-60 years old) was around 20%. The analysis of SARS-CoV-2 infection age distribution showed that middle-aged adults accounted for 54.7% of SARS-CoV-2 positive persons, followed respectively by young adults (33.7%), children (7.7%) and elderly (3.8%). 68% (N = 402) of SARS-CoV-2 infected persons were asymptomatic, 26.3% (N = 156) had influenza-like symptoms, 2.7% (N = 16) had influenza-like symptoms associated with anosmia and ageusia, 2% (N = 11) had dyspnea and 1% (N = 7) had respiratory failure, which resulted in death. Data also showed that 12% of SARS-CoV-2 infected subjects, had chronic diseases. Hypertension, diabetes, and asthma were the top concurrent chronic diseases representing respectively 58%, 25% and 12% of recorded chronic diseases. Half of SARS-CoV-2 RT-PCR positive patients were cured within 14 days following the initiation of the anti-COVID-19 treatment protocol. 78.3% of COVID-19 patients and 55% of SARS-CoV-2 RT-PCR confirmed negative contact-cases were positive for anti-SARS-CoV-2 antibodies. Patients with severe-to-critical illness have higher leukocytes, higher neutrophils and lower lymphocyte counts contrarily to asymptomatic patients and patients with mild-to-moderate illness. Neutrophilic leukopenia was more prevalent in asymptomatic patients and patients with mild-to-moderate disease for 4 weeks after diagnosis (27.1-42.1%). In Patients with severe-to-critical illness, neutrophilic leukocytosis or neutrophilia (35.6-50%) and lymphocytopenia (20-40%) were more frequent. More than 60% of participants were blood type O. It is also important to note that infection rate was slightly higher among A and B blood types compared with type O. In this African setting, young and middle-aged adults are most likely driving community transmission of COVID-19. The rate of critical disease is relatively low. The high rate of anti-SARS-CoV-2 antibodies observed in SARS-CoV-2 RT-PCR negative contact cases suggests that subclinical infection may have been overlooked in our setting.

Increased platelets count in HIV-1 uninfected infants born from HIV-1 infected mothers.

HIV-exposed uninfected infants (HEU) represent a growing population in developing countries including Gabon. Several studies have shown the vulnerability of these infants toward infectious diseases. The aim of the study was to contribute to the global effort to understand how HIVexposure or anti retroviral therapy affects infants' blood elements. We assessed HEU infants' complete blood count using a blood analyzer instrument. Our investigations showed that among the observed clinically relevant hematological abnormalities events, thrombocytosis was the most prevalent clinically relevant hematological abnormality associated with HEU infants'. We showed that HEU infants had significantly higher platelets count than HUinfants. Therefore, higher level of platelets seems to characterize HEU infants when compared to HU infants.

M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

Tuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response to M. tuberculosis infection, we conducted a cross-sectional study investigating M. tuberculosis infection status and comparing the release profiles of cytokines GM-CSF, IFN-γ, IL-1ß, IL-10, IL-12 (p70), IL-2, IL-4, IL-5, IL-6, IL-8, TNF-α, in community controls (CCs) and healthy healthcare workers (HCWs) highly exposed to TB. Among HCWs and CCs, the probability of latent M. tuberculosis (LTB+) infection was respectively 5.4 (p = 0.002) and 3.4 (p = 0.006) times higher in men than women. The odds ratio of LTB infection was 4 times higher among HCWs in direct contact with active TB patients than other HCW (p = 0.01). Whole blood supernatant cytokine responses to M. tuberculosis antigens showed differential pro-inflammatory responses between HCWs and CCs. CCsLTB- had higher IL-1ß responses than HCWsLTB- (p = 0.002). HCWsLTB+ had significantly higher IL-8 responses to M. tuberculosis antigens than HCWsLTB- (p = 0.003) and CCsLTB- (p = 0.015). HCWsLTB+/- showed weak but positive TNF-α responses to M. tuberculosis antigen stimulation compared to CCsLTB+/- (p ≤ 0.015). Looking at T-helper (1 and 2) responses, HCWsLTB+ and CCsLTB+ had significantly higher IFN-γ and IL-2 responses compared to HCWsLTB- and CCsLTB- (p < [0.0001-0.003]). Also, TB antigen induced IL-5 secretion was significantly higher in HCWsLTB+ and CCsLTB+ than in non-infected CCsLTB- (p < [0.005-0.04]). M. tuberculosis antigen specific responses in HCWsLTB+ varied based on active TB exposure gradient. HCWsLTB+ who were highly exposed to active TB (≥3 hours per day) had significantly higher IFN-γ and IL-8 responses (p ≤ 0.02) than HCWs LTB+ not in direct contact with active TB patients. HCWsLTB+ working with active TB patients for 5 to 31 years had a significantly enhanced secretion of proinflammatory cytokines (GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-8, IL-12p70, TNF-α) compared to HCWsLTB- (p < [0.0001-0.01]). Secretion of anti-inflammatory/Th2 cytokines IL-5 and IL-10 was also higher in HCWsLTB+ than HCWsLTB-. In conclusion, LTBI individuals controlling the M. tuberculosis infection have an enhanced TB specific Th1-cytokines/proinflammatory response combined with selected Th2 type/anti-inflammatory cytokines induction.

Publisher Correction: M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Altered Toll-Like Receptor-4 Response to Lipopolysaccharides in Infants Exposed to HIV-1 and Its Preventive Therapy.

Pathogen sensing and recognition through pattern recognition receptors, and subsequent production of pro-inflammatory cytokines, is the cornerstone of the innate immune system. Despite the fact that HIV-exposed uninfected (HEU) infants are prone to serious bacterial infections, no study has focused on the functionality of their bacteria recognition system. This is the first study to investigate baseline levels of three critically important immune response molecules in this population: complement component (C)-3, toll-like receptor (TLR)-4, and C-reactive protein (CRP). We enrolled 16 HEU and 6 HIV-unexposed (HU) infants. TLR4 function was investigated by stimulating whole blood with increasing concentrations of TLR4-agonist ultrapure lipopolysaccharides. TLR4/TLR4-agonist dose response were assessed by measuring IL-6 secretion. Complement C3 and CRP were measured by photo spectrometry. Data showed no significant differences in baseline concentration of CRP between HEU and HU infants. Complement C3 was significantly higher in HEU infants than HU infants. TLR4 anergy was observed in 7 of 12 HEU infants, whereas the rest of HEU infants (n = 4) and the control HU infants tested (n = 3) showed responsive TLR4. None of the HEU infants investigated in this study had severe infections in the year after their birth. In conclusion, TLR4 anergy can occur in HEU infants without necessarily translating to increased vulnerability to infectious diseases.